Project Summary Sensory over-responsivity (SOR), the unusual negative response to typically non-noxious stimuli, represents a prominent feature of many neurodevelopmental conditions, including Autism Spectrum Disorder (ASD), Anxiety, Attention Deficit/Hyperactivity, and Developmental Coordination Disorders. SOR severely disrupts all aspects of a child's development, including the ability to learn and socially engage. Despite growing recognition of SOR as a core feature in neurodevelopmental conditions, the neural mechanisms of SOR remain unclear. As a result of this gap, SOR has historically been thought to be ?behavioral? or due to ?bad parenting? or a consequence of ?having autism?. This percept has been challenged by data from our lab and others showing white matter microstructural and functional imaging differences in children with sensory processing dysfunction (SPD) and in children with ASD/SOR. Delineating the underlying neural networks that subserve SOR, both auditory and tactile, will not only guide our understanding of this condition, but also shift the conceptualization of SOR to that of a treatable neurologic condition. Obtaining the neural signature of SOR will contribute to finding a biomarker for neural remodeling with cognitive training paradigms similar to what we have piloted in the domain of cognitive control. Our work utilizing in-lab direct assessment of auditory SOR will test the scientific premise that SOR results from the disconnection of a higher-order SOR network: the Posterior Corona Radiata, Superior Longitudinal Fasciculus, and the Cingulate Bundle. We will further determine whether this putative SOR network reflects a general vulnerability in the posterior periventricular regions, which are rich in highly connecting white matter tracts, or is specific to auditory SOR. Furthermore, if this microstructural disconnection is SOR specific, then is it a multi-domain SOR network or does each sensory domain (e.g. auditory and tactile) rely on a unique set of connections-- as is suggested by the non-overlapping sensory domain phenotypes in affected children? A multifaceted phenotype and neuroimaging approach is required to answer these questions. The objective of this proposal is to advance our direct assessment of sensory related behavior and apply novel structural neuroimaging methods to elucidate the neural architecture of SOR using an RDoC approach. To achieve this goal, we will assess auditory and tactile SOR using the Sensory Processing: Three Dimensions Assessment (SP-3D:A) paired with innovative structural imaging, Neurite Orientation Dispersion and Density Imaging, for detailed microstructural assessment, and Edge Density Imaging, for advance connectome assessment, in 170 children, ages 8-12 years, with neurodevelopmental concerns. All phenotype and neuroimaging data will be made available to the field in order to support ongoing understanding of sensory processing in this unique data set.